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Over the past decade, the understanding of NoV immunology has grown immensely. Studies of the natural immune response to NoV in humans and animal models have laid the foundation for innovations in cell culture systems for NoV and development of new therapeutics. Evidence from animal models, NoV surrogates, observational human research, and human challenge studies suggest that the innate immune response is critical for limiting NoV infection but is insufficient for viral clearance. NoV may antagonize the innate immune response to establish or prolong infection. However, once a robust adaptive immune response is initiated, the immune system clears the infection through the action of T and B cells, simultaneously generating highly specific protective immunologic memory. We review here both the current knowledge on NoV immunity and exciting new developments, with a focus on ongoing vaccine development work, novel cell culture systems, and advances in understanding the role of the gut microbiome. These changes reinforce the need for a better understanding of the human immune response to NoV and suggest novel hypotheses.<\/jats:p>","DOI":"10.1002\/eji.201545512","type":"journal-article","created":{"date-parts":[[2015,8,10]],"date-time":"2015-08-10T11:59:38Z","timestamp":1439207978000},"page":"2742-2757","source":"Crossref","is-referenced-by-count":53,"title":["Norovirus immunology: Of mice and mechanisms"],"prefix":"10.1002","volume":"45","author":[{"given":"Kira L.","family":"Newman","sequence":"first","affiliation":[{"name":"Department of Epidemiology Rollins School of Public Health Emory University Atlanta GA USA"},{"name":"Medical Scientist Training Program Emory University School of Medicine Atlanta GA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan S.","family":"Leon","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Rollins School of Public Health Emory University Atlanta GA USA"},{"name":"Hubert Department of Global Health Rollins School of Public Health Emory University Atlanta GA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,8,25]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(14)70767-4"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMsa1206589"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0950268812000799"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2012.14023"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-12-325886"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1086\/591627"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-010-0965-4"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61689-4"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61728-0"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60222-6"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61698-6"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0072788"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2012.102"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0b013e31818255cc"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jis942"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/1469-0691.12722"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/0141076813511450"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01535-14"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2014.05.015"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4463"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1017\/erm.2014.2"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.13.109"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOG.0000000000000022"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2014.05.021"},{"key":"e_1_2_11_26_1","first-page":"977","volume-title":"Virus taxonomy: classification and nomenclature of viruses\u2014ninth report of the International Committee on Taxonomy of Viruses","author":"Clarke I. 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